Connective tissue I 2024 http://www.anatomybox.com/wp-content/uploads/2012/11/connective-tissue.jpg http://stevegallik.org/sites/histologyolm.stevegallik.org/images/areolar_01.jpg Connective tissue proper Obsah obrázku text, Písmo, snímek obrazovky, Grafika Popis byl vytvořen automaticky pvanhara@med.muni.cz Petr Vaňhara Epithelial tissue Tissue classification is based on morphology and function: Myofibrils à contraction Mesoderm – skeletal muscle, myocard, mesenchyme – smooth muscles Neurons and neuroglia Reception and transmission of electric signals Ectoderm Dominant extracellular matrix Connective tissue, cartilage, bone… Mesenchyme Continual, avascular layers of cells with different function, oriented to open space, with specific junctions and minimum of ECM and intercellular space. Derivates of all three germ layers http://www.arthursclipart.org/medical/humanbody/muscle%20tissue.gif http://djpowell.files.wordpress.com/2009/02/neuron-network.jpg http://www.technion.ac.il/~mdcourse/274203/slides/Connective%20%20Tissue/2-Loose%20Connective%20Tis sue-A.jpg http://www.temple.edu/dentistry/admissions/Images/epithelium.jpg CONTEMPORARY TISSUE CLASSIFICATION Connective tissue Nerve tissue Muscle tissue Various functions of connective tissues depend on its mechanical and biological properties •surrounds other tissues and provides structural support •compartmentalization •physical-chemical environment •nutrition •innervation •immunological support •storage of energy •cell signaling and tissue regeneration CONNECTIVE TISSUE Obsah obrázku kresba, skica, umění Popis byl vytvořen automaticky ECM Fibrous component •collagen fibers (prototypically col. I, II) •reticular •elastic Amorphous component (ground substance) Complex matrix consisting of •glycosaminoglycans •glycoproteins •proteoglycans All tissues are composed of cells and extracellular matrix In connective tissue, the ECM is dominant GENERAL COMPOSITION OF CONNECTIVE TISSUE Cells Permanent and temporary cell populations •fibroblasts/myofibroblasts •immune cells •phagocytes •adipocytes •adult stem cells •specialized cells of cartilage (chondroblasts/chondrocytes) •specialized cells of bone •(osteoblasts/osteocytes/osteoclasts) Specific composition and properties is dependent on the tissue type (connective ´ ligament ´ cartilage ´ bone) GENERAL CLASSIFICATION OF CONNECTIVE TISSUE Permanent •Fibroblasts/fibrocytes/myofibroblasts •Adipocytes •Adult stem cells Transiet (migratory) •Macrophages of c.t. /histiocytes) •Mast cells •Plasma cells •Lymphocytes, granulocytes •… CELLS OF CONNECTIVE TISSUE PROPER Obsah obrázku text, diagram, mapa Popis byl vytvořen automaticky Cells of c.t. proper CELLS OF CONNECTIVE TISSUE PROPER Obsah obrázku plíseň Popis byl vytvořen automaticky Obsah obrázku skica, kresba, umění Popis byl vytvořen automaticky •Principal c.t. cells •ECM producers •Originate from mesenchyme and resides in the c.t. permanently •Lack typical epithelial polarity •Migration •Fibrocyte « fibroblast •Myofibroblasts •Different tissues contain fibroblasts with different biological properties • Fibroblasts CELLS OF CONNECTIVE TISSUE PROPER Obsah obrázku text, snímek obrazovky, design Popis byl vytvořen automaticky Migration of fibroblasts CELLS OF CONNECTIVE TISSUE PROPER https://www.sciencephoto.com/media/1232046/view/fibroblast-tem CELLS OF CONNECTIVE TISSUE PROPER Obsah obrázku Organismus, text, Mořští bezobratlí Popis byl vytvořen automaticky DOI: 10.1038/nrm809 10.1164/ajrccm.161.5.9903102 •Features of fibroblasts and smooth muscle cells •Contractile cellular structures composed of actin microfilaments and myosin •Wound closure and healing Myofibroblasts Obsah obrázku plíseň, černobílá Popis byl vytvořen automaticky CELLS OF CONNECTIVE TISSUE PROPER •Histiocytes •Derived from circulating monocytes (monocyte-macrophage mononuclear system) •Phagocytosis •Immunomodulation Obsah obrázku houba, plíseň Popis byl vytvořen automaticky Macrophages CELLS OF CONNECTIVE TISSUE PROPER •Large, oval, 20-30mm •Similar to other leukocytes with granules, but it is tissue resident •Granules –heparin –histamine –serine proteases (inflammation regulators) –eosinophil and neutrophil chemoattractants –leukotriens •Perivascular and mucosal mast cells • T. Clark Brelje and Robert L. Sorenson, Minneapolis, Minnesota, USA. •Mediators of immediate hypersensitivity reaction Mast cells CELLS OF CONNECTIVE TISSUE PROPER •Large, ovoid cells •derived from B-lymphocytes •Basophilic cytoplasm – RER •Clockface nucleus (alternating heterochromatin and euchromatin) •Produce antibodies (immunoglobulins) •Short lifespan (10-20 days) T. Clark Brelje and Robert L. Sorenson, Minneapolis, Minnesota, USA. Obsah obrázku umění, kresba, černobílá, potisk Popis byl vytvořen automaticky https://www1.udel.edu/biology/Wags/histopage/histopage.htm Plasma cells •Mesenchymal origin •Adult tissues •Differentiate to many cells of CT • CELLS OF CONNECTIVE TISSUE PROPER Výsledek obrázku pro mesenchymal stem cells Obsah obrázku diagram Popis byl vytvořen automaticky Mesenchymal stem (stromal) cells DERIVATIVES OF MESENCHYME Sources of mesenchymal stem cells. | Download Scientific Diagram Mesenchymal stem (stromal) cells •Mesenchymal stem cells are different in different tissues •Mesenchymal stem cells are important tools for tissue engineering and understanding tissue biology Výsledek obrázku pro mesenchymal stem cells Výsledek obrázku pro mesenchymal stem cells CELLS OF CONNECTIVE TISSUE PROPER Mesenchymal stem (stromal) cells MESENCHYMAL STEM CELLS – CLINICAL CONTEXT DOI: 10.3389/fsurg.2015.00001 POTENTIAL APPLICATIONS OF MESENCHYMAL STEM CELLS https://doi.org/10.3389/fbioe.2020.00043 ECM = fibers + ground substance • ECM OF CONNECTIVE TISSUE PROPER Obsah obrázku text, diagram, snímek obrazovky, mapa Popis byl vytvořen automaticky ECM OF CONNECTIVE TISSUE PROPER Composition of ECM determines biochemical and biophysical properties of c.t. ECM of connective tissue is produced by fibroblasts (or chondrocytes, osteoblasts). However, specific ECM can be produced by virtually any cell of our body (eg. epithelial and muscle cells producing basal lamina). ECM OF CONNECTIVE TISSUE PROPER Obsah obrázku text, diagram, mapa Popis byl vytvořen automaticky Extracellular matrix Fibrous component •Collagen fibers (e.g. col. I, II) •Reticular •Elastic Amorphous component (ground substance) Complex matrix consisting of •Glycosaminoglycans •Glycoproteins •Proteoglycans Fibers • ECM OF CONNECTIVE TISSUE PROPER Obsah obrázku text, diagram, snímek obrazovky, mapa Popis byl vytvořen automaticky Collagen fibers • •family of fibrous proteins encoded by >35 genes •polymer – subunit = procollagen and tropocollagen; triple helix •different structural and mechanical properties (strength, elasticity, pliability…) •most abundant protein in human body ( 30% dry weight) http://www.arserrc.gov/ctmi/1948collagen.gif EXTRACELLULAR MATRIX – FIBROUS COMPONENT •Polyribosomes bind to RER and synthetize peptide chains a1 a a2 (~250 AA, 28kDa) •In RER peptide chains are modified (hydroxylation of proline and lysine – co-factor vitamin C) Chains assemble into triple helix - procollagen •In GA, procollagen is further modified and secreted from cells EXTRACELLULAR MATRIX – FIBROUS COMPONENT Collagen synthesis • D:\Documents\Science\Výuka\Histology Resources\Connective Tissue\Netter's Histology\Collagen.jpg EXTRACELLULAR MATRIX – FIBROUS COMPONENT further study: https://www.ncbi.nlm.nih.gov/books/NBK507709/ Procollagen is then modified to tropocollagen (by procollagenpeptidase) Tropocollagen is organized to higher fibrillar structures in ECM (fibrils, fibers) Individual collagen molecules are connected (lysyloxidases) Collagen synthesis • EXTRACELLULAR MATRIX – FIBROUS COMPONENT Collagen synthesis • CLINICAL CONTEXT Obsah obrázku Lidská tvář, oblečení, osoba, obraz Popis byl vytvořen automaticky Obsah obrázku Zub, jazyk, zuby, osoba Popis byl vytvořen automaticky Autor: BIOPHOTO ASSOCIATES/SCIENCE PHOTO LIBRARY James Lind 1747 Type Localization Structure Main function I Bone, tendons, meniscus, dentin, dermis, capsules of organs, loose CT 90% of type I Fibrils (75nm) – fibers (1-20mm) Resilience in pull II Hyaline and elastic cartilage Fibrils (20nm) Resilience in pressure III Skin, veins, smooth muscles, uterus, liver, spleen, kidney, lung Like I, high content of proteoglycans and glycoprotiens, reticular network Shape formation IV Basal lamina of epithelium and endtohelium, basal membranes No fibrils or fibers Mechanical support V Lamina of muscle cells and adipocytes, fetal membranes Like IV VI Interstitial tissue, chondrocytes – adhesion Connecting dermis and epidermis VII Basal membrane of epithelium VIII Some endothelia (Cornea) IX, X Growth plate, hypertrophic and mineralized cartilage Growth of bones, mineralization COLLAGEN FAMILY aza_005 HP_img6-15-6a HP_img6-15-6 AZAN HES HE COLLAGEN IN LIGHT MICROSCOPE File:Unraveling Collagen.jpg I. Julian Voss-Andreae "Unraveling Collagen" 2005 Orange Memorial Park Sculpture Garden, City of South San Francisco, CA COLLAGEN IN ART •less abundant than collagen •polymer – tropoelastin •minimal tensile resistance, loss of elasticity if overstretched •reduction of hysteresis = allow return back to original state after mechanic change •staining – orcein, aldehyde fuchsin http://legacy.owensboro.kctcs.edu/gcaplan/anat/Histology/elastic.gif http://www.udel.edu/Biology/Wags/histopage/empage/ect/ect3.gif EXTRACELLULAR MATRIX – FIBROUS COMPONENT Elastic fibers • Elastic fibers • Obsah obrázku text, zelenina Popis byl vytvořen automaticky Elastin • Collagen • EXTRACELLULAR MATRIX – FIBROUS COMPONENT Elastic fibers • Obsah obrázku text, venku, území Popis byl vytvořen automaticky Obsah obrázku bílé, čokoláda Popis byl vytvořen automaticky •Similarly to collagen, elastin precursors are secreted and polymerize •Deposition of elastin aggregate along fibers of protein fibrillin •Amount of fibrillin (nonelastic) and elastin (elastic) determines elasticity of CT Fibrillin • Elastin • Elastin • EXTRACELLULAR MATRIX – FIBROUS COMPONENT •collagen 3D meshwork •bone marrow, spleen, lymphatic nodules •microenvironment for e.g. hematopoietic stem cells and progenitors • Obsah obrázku text, látka Popis byl vytvořen automaticky EXTRACELLULAR MATRIX – FIBROUS COMPONENT Reticular fibers • RETICULAR CONNECTIVE TISSUE 0072_0001 Ground substance • ECM OF CONNECTIVE TISSUE PROPER Obsah obrázku text, diagram, snímek obrazovky, mapa Popis byl vytvořen automaticky •Amorphous extracellular matrix •Colorless, transparent, homogenous substance consisting of: glycosaminglycans, proteoglycans and structural glycoproteins image010 EXTRACELLULAR MATRIX – GROUND SUBSTANCE Ground substance • •linear polysaccharides composed of two disaccharide subunits – uronic acid and hexosamine http://de.academic.ru/pictures/dewiki/72/Hyaluronsaure.png glucosamin or galactosamin glucuronic or iduronic acid EXTRACELLULAR MATRIX – GROUND SUBSTANCE Glycosaminoglycans (GAGs) • • •linear polysaccharides composed of two disaccharide subunits – uronic acid and hexosamine EXTRACELLULAR MATRIX – GROUND SUBSTANCE https://doi.org/10.3390/cancers15010266 Glycosaminoglycans (GAGs) • Glycosaminoglycan Localization Hyaluronic acid Umbilical cord, synovial fluid, fluid of corpus vitreum, cartilage Chondroitinsulfate Cartilage, bone, cornea, skin, notochord, aorta Dermatansulfate Skin, ligaments, adventitia of aorta Heparansulfate Aorta, lungs, liver, basal membranes Keratansulfate Iris, cartilage, nucleus pulposus, anulus fibrosus bind to proteins (except for hyaluronic acid) EXTRACELLULAR MATRIX – GROUND SUBSTANCE Glycosaminoglycans (GAGs) • CLINICAL CONTEXT •glycosaminoglycans = acid mucopolysaccharides (polysaccharides rich in hexosamines) • •group of rare genetic diseases – mucopolysaccharidoses –autosomal recessive disease caused by mutation in genes coding for enzymes of GAG metabolism –broad spectrum of problems –typical symptoms – craniofacial dysmorphia, cardiomyopathy, splenomegaly, slow growth and psychomotor development – Obsah obrázku text, snímek obrazovky, Písmo, číslo Popis byl vytvořen automaticky •protein core + dominant linear saccharide component •proteoglycan aggregates •water-binding, volume dependent of hydratation • • aggrecan (cartilage) • syndecan • fibroglycan • EXTRACELLULAR MATRIX – GROUND SUBSTANCE Proteoglycans • dominant protein + branched saccharide component • interaction between cells and ECM http://www.fz-juelich.de/cae/servlet/contentblob/899194/normal/3412/NWG_Glykosylierung.jpg ― fibronectin – connects collagen fibers and glykosaminoglycans, cell adhesion and migration ― laminin – basal lamina – epithelial integrity ― chondronectin – cartilage – adhesion of chondrocytes to collagen EXTRACELLULAR MATRIX – GROUND SUBSTANCE Obsah obrázku světlo, Barevnost, zelené, Výrazná modrá Popis byl vytvořen automaticky human mesenchymal stem cells (MSC), BD, Alexa Fluor® 488 Mouse Anti-Fibronectin Structural glycoproteins Glycoproteins vs. proteoglycans EXTRACELLULAR MATRIX – GROUND SUBSTANCE COMPOSITION OF ECM COMPOSITION OF ECM Cell – ECM interactions HISTOLOGICAL CLASSIFICATION OF CT PROPER vaz 6 Embryonic mesenchyme Wharton’s jelly Embryonic: •Embryonic mesenchyme and mucous c.t. (Wharton’s jelly) of umbilical cord Postnatal (adult): •Loose collagen c.t. (areolar, interstitial) •Dense collagen regular and irregular c.t. •Elastic c.t. •Reticular c.t. •Adipose c.t. HISTOLOGICAL CLASSIFICATION OF CT PROPER HP_img6-15-6a •Permanent fibroblasts, macrophages (histiocytes), occasionally adipocytes •Other transient cell types (leukocytes) •Collagen and elastic fibers •Amorphous ground substance is dominant •Most abundant type of CT •Rich vascularization and innervation •Walls of hollow organs, interstitium, mucosal and submucosal CT http://medsci.indiana.edu/a215/virtualscope/docs/chap2_1.htm Loose collagen c.t. HISTOLOGICAL CLASSIFICATION OF CT PROPER Difference Between Dense Regular and Dense Irregular Connective Tissue Dense collagen c.t. HISTOLOGICAL CLASSIFICATION OF CT PROPER Obsah obrázku vzor, látka Popis byl vytvořen automaticky Elastic membranes of aorta Lig. flava HE 50X Weigert, 50X Elastic c.t. 0072_0001 HISTOLOGICAL CLASSIFICATION OF CT PROPER Niche for immune cells Reticular c.t. •Adipocytes, fibroblasts, reticular, collagen and elastic fibers, capillaries •White and brown adipose tissue • HISTOLOGICAL CLASSIFICATION OF CT PROPER Adipose c.t. • rich vascularization • unilocular adipocytes with only one lipid droplet • endocrine activity - leptins (adipokinins) HISTOLOGICAL CLASSIFICATION OF CT PROPER 10.1038/s42255-019-0095-y White adipose c.t. • small cells with numerous fat droplets • typical localization – between shoulder blades, axilla, mediastinum, around kidneys, pancreas, small intestine • fetus and children up to 1st year of life • fast source of energy HISTOLOGICAL CLASSIFICATION OF CT PROPER Image result for hibernation dormouse Brown adipose c.t. •Mesenchyme = loose tissue between germ layers •Complex network of small, undifferentiated star- or spindle-shaped cells •Jelly-like amorphous ground substance rich in hyaluronic acid •Origin in mesoderm (=germ layer) or neural crest http://www.mun.ca/biology/desmid/brian/BIOL3530/DB_Ch02/fig2_13.jpg http://www.mun.ca/biology/desmid/brian/BIOL3530/DB_Ch02/DBNModel.html Trilaminar germ disc http://embryology.med.unsw.edu.au/wwwhuman/Stages/Images/CSt9b.gif EMBRYONIC ORIGIN OF CONNECTIVE TISSUE Mesenchyme Connective Bone Cartilage http://www.mun.ca/biology/desmid/brian/BIOL3530/DB_Ch02/fig2_13.jpg Mesenchyme EMBRYONIC ORIGIN OF CONNECTIVE TISSUE C.t. derivatives of mesenchyme MESENCHYME Obsah obrázku text, snímek obrazovky, diagram Popis byl vytvořen automaticky Mesenchyme as embryonic c.t. and a cellular phenotype - •Embryonic mesenchyme – undifferentiated embryonic cell population Term from embryology •Mesenchymal phenotype – set of cell properties: ECM production and remodeling, migration, absence of epithelial polarity and intercellular junctions Term from cell biology https://doi.org/10.1172/JCI39104. SUMMARY OF CONNECTIVE TISSUE Collagen Structure Function and distribution Loose collagen CT Abundant ground substance, collagen fibers with random arrangement Microvascularisation Innervation Irregular dense collagen CT Few ground substance, few cells, many collagen fibers, random arrangement Mechanically resistant organ capsules Regular dense collagen CT Tightly arranged collagen fibers with fibroblasts intercalated between them Part of musculoskeletal system. Tendons, ligaments Embryonic Mesenchyme Undifferentiated cells uniformly dispersed in ground substance, few collagen fibers Undifferentiated progenitors Wharton’s jelly Viscous amorphous matrix with collagen fibers. ECM-producing stromal cells with MSC properties. Matrix of umbilical cord Special Reticular CT Network of collagen III fibers and reticular cells Support of hematopoietic and lymphatic cells Elastic Rich in elastic fibers Lig. flava, lig. vocale. Lung interstitium, flexible support to elastic arteries and aorta Adipose Adipocytes Energy storage (white fat), heat production (brown fat) Cartilage Chondroblasts, chondrocytes Mechanical support Bone Osteoblasts, ostecoytes, osteoclasts Mechanical support, calcium and phospate metabolism Blood See lecture on blood & hematopoiesis this semester Guide to General Histology and Microscopy Anatomy FURTHER STUDY http://www.histology.med.muni.cz Thank you for attention pvanhara@med.muni.cz